Chromatographic processes enable the separation and purification of chemical, fine-chemical, biological and pharmaceutical products. Compared to other thermal separating processes, they have the particular advantage that they can be performed at moderate and hence product-protective temperatures (M. Juza, M. Mazzotti and M. Morbidelli, Trends in Biotechnology, 18, 2000, pages 108-118; S. Imamoglu, Advances in Biochemical Engineering/Biotechnology, 76, 2002, pages 211-231). In many applications, especially in the lifescience sector, the high purity requirements attached to the end products can additionally often only be achieved with the aid of chromatographic processes (M. Schulte and J. Strube, Journal of Chromatography A 906, 2001, pages 399-416).
The so-called batchwise process is widespread. It is particularly flexible and technically comparatively simple to build. In successive cycles, a finite pulse of the substance mixture to be separated is in each case applied to the chromatographic column. Thereafter, elution is effected with one or more solvents. The different components are adsorbed to different degrees as the mixture flows through the chromatographic column, are separated as a consequence and are fractionated at the outlet of the column. This is followed by a phase of fixed bed regeneration. A new batch cannot be started until either the preceding batch has ended or the most strongly adsorbable component of the preceding batch has migrated sufficiently far in order not to be overtaken by the more weakly adsorbable component. The batchwise process therefore generally takes a lot of time to purify a given amount of product.
In addition to the batchwise method, there exist continuous alternatives which find use principally in medium scale and in industrial scale production (B. Clay, Chemical Market Report 259, 2001, page 15). They generally have lower solvent consumption and allow higher productivity. The principle of continuous countercurrent chromatography is known from M. Negawa and F. Shoji, Journal of Chromatography 590, 1992, pages 113-117. Suitable units for performing continuous countercurrent chromatography, especially the so-called simulated moving bed (SMB) units, are described, for example, in U.S. Pat. No. 2,621,149 B; U.S. Pat. No. 2,985,589 B and are commercially available.
In general, in an SMB unit, a plurality of individual columns are bonded to form a closed circuit. At one point in the circuit, feed is supplied, which generally comprises a binary mixture (A+B). At a further point in the circuit, pure solvent is supplied. The internal concentration profile which arises for the A+B mixture is established after a startup phase. The more weakly adsorbing component (A) is drawn off in the so-called raffinate outlet, while the more strongly adsorbable component (B) is obtained in the extract outlet. In the course of operation of the SMB unit, the inlets and outlets are relayed via valves, for example single valves, multiway valves, valve blocks, flaps or rotary valves, periodically, but not necessarily simultaneously, in the direction of liquid flow, such that a countercurrent motion of liquid stream and stationary phase appears to arise. The zones identified in the SMB process between the particular inlets and outlets have the following roles in the overall separation process:    Zone I: Desorption of the strongly adsorbable component (A),    Zone II: Desorption of the weakly adsorbable component (B),    Zone III: Adsorption of the strongly adsorbable component (A),    Zone IV: Adsorption of the weakly adsorbable component (B).
In the patent literature, a series of developments of the simulated moving bed process can be found, mainly with the aim of achieving better separating performances and/or of extending the process to multisubstance separations.
In the patent U.S. Pat. No. 6,712,973 B, for example, an asynchronous switching of the inlet and outlet sites is undertaken, which gives rise to additional degrees of freedom for influencing the mean zone lengths. The patent U.S. Pat. No. 5,102,553 B patents a method in which the volume flows can be altered during a switching period, as a result of which the product withdrawal, both in the extract and in the raffinate, can be adjusted better to the course of the axial concentration profile with time. H. Schramm, M. Kaspereit and A. Seidel-Morgenstern, Journal of Chromatography A 1006, 2003, pages 77-86 additionally propose modulation of the feed concentrations, which leads to a significant increase in the productivity. The economic advantage over the conventional SMB method is, in this case, however, greatly restricted by the solubility limits of the substance mixture in the eluent. U.S. Pat. No. 6,602,420 B finally describes a method for purifying sucrose with the aid of the SMB process, in which the so-called displacement effect is utilized. The displacement effect here describes the property of the components of highly concentrated solutions to mutually displace one another owing to interaction mechanisms, which results in an additional separating effect.
Further processes known in the patent literature are ISMB and SSMB. In the so-called improved SMB process (ISMB), as the main difference from the conventional SMB process, the input and output are decoupled from the recycling (D. Costesson, G. Rearick and M. Kearne, Zucker-industrie 125, 2000, pages 333-335). Once the feed and eluent have been supplied and the raffinate and extract have been removed, pure recycling takes place. Subsequently, the ports are switched synchronously one column further in flow direction. The energy requirement of the recycling phase is a dominating factor in the overall costs of industrial scale units. This can be reduced in the ISMB process, since the recycling pump does not deliver permanently (F. Lutin, M. Bailly and D. Bar, Desalination 148, 2002, pages 121-124). The sequential SMB process (SSMB) is designed for the recovery of several fractions of a substance mixture and is used exclusively in the sugar industry (S. Baudouin and X. Lancrenon, Industries Alimentaires et Agricoles, 120, 2003, pages 42-48). Similarly to the SMB process, several columns are arranged in a closed circuit. In contrast to the conventional SMB method, the input and output are configured in a discontinuous manner. Furthermore, feed can be supplied at several points in the circuit. The product streams can likewise be collected at any time at the outlet of every column. The recycling of impure fractions can be effected either in the same column or in an adjacent column. SSMB corresponds to an intelligent arrangement of a plurality of batch columns, is basically a batchwise process and only partly utilizes the advantages of a simulated countercurrent. What additionally results is a complex scheduling problem which has to be solved for the optimal operation of such units.
The patent U.S. Pat. No. 6,805,799 presents a new “SMB focusing” method, with whose aid multisubstance mixtures can be separated in an “SMB unit”. In this case, a gradient profile is achieved by establishing differences, for example, in salt content or pH from zone to zone. As a result, only one component should elute at the outlet of each zone. Feed is applied in the first zone and the components are obtained gradually according to their elution power in the particular zones. Similarly to the SSMB process, the countercurrent effect is not utilized here. This structure corresponds, if anything, to a coupled operation of a plurality of batch columns. The use of this method is restricted to separation problems in which an additional external influencing factor, for example (salt content or pH), can be found on the separating action. Furthermore, a significant gradient has to be formed.
The conventional SMB process and all continuous extensions known to date (VARICOL, PowerFeed, ModiCon, ISMB, etc.) can in principle only be used for binary separating tasks. Even the recovery of one component from a mixture is possible only when the latter is the most strongly or the most weakly adsorbable component. This is a disadvantage compared to batchwise operation, which thus enables more flexible operation. This is the reason why the majority of industrial uses are in the batchwise operation.
Owing to the fact that the conventional SMB process can divide a multisubstance mixture only into two fractions, its application to multisubstance separations entails the utilization of a plurality of SMB units which are arranged, for example, in a cascade. Patent U.S. Pat. No. 6,602,420 B describes, for example, the industrial recovery of sucrose with a cascade of two SMB units. However, this means a considerable capital investment. It is more economically favorable to operate a single SMB unit in which the individual separating steps are performed successively in time until the multisubstance mixture has been separated into its individual constituents. However, this is associated with high production complexity and time demand. In this case, SMB technology, however, loses the advantages over batchwise operation with regard to productivity and solvent consumption which have been praised to date.
In addition to batch chromatography, in the separation of multisubstance mixtures, so-called annular chromatography has also become established (Finke et al., J. Agric. Food Chem., 50, 2002, pages 185-201; F. Hilbrig, Journal of Chromatography B, 790, 2003, pages 1-17). In annular chromatography, the feed is supplied at a fixed location to a rotating column, while eluent is introduced to the remaining circumference. As a result of the rotation of the chromatographic column, bands form and elute at different angles. It is thus possible to separate a multisubstance mixture into its individual constituents. In annular chromatography, the separation is effected, in spite of the radial motion, mainly in axial direction. The annular chromatography therefore corresponds to a batch process with many columns arranged in a circle. At the same time, very high amounts of solvent are required. Difficulties in the distribution of the solution at the top and the accumulation of the products at the bottom of a CAC (continuous annular chromatography) unit are known, and uniform input and output of the components to and from a rotating column constitute an engineering challenge which has not been solved satisfactorily to date for a large unit with correspondingly high throughput. However, the possibility of continuously separating a multisubstance mixture is advantageous.
There is therefore an urgent need for a chromatographic process which enables the separation of binary and multisubstance mixtures, and the process should be employable economically in a single unit.